crossing96/oncoscreening huggingface dataset:
Radiotherapy plus pembrolizumab for advanced urothelial carcinoma: results from the ARON-2 real-world study.	The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival.	bladder
[German expert consensus on programmed cell death ligand 1 (PD-L1) testing in perioperative systemic therapy of muscle invasive bladder cancer].	The risk of recurrence in patients with muscle invasive bladder cancer (MIBC) after radical cystectomy depends on the pathological tumor stage. In particular, patients with lymph node metastasis (pN+), locally advanced (≥pT3), or residual muscle invasive tumor despite neoadjuvant chemotherapy are at high risk. Currently, the importance of adjuvant therapy with immune checkpoint inhibitors is increasing in the context of perioperative systemic therapeutic concepts. The indication for the PD‑1 inhibitor nivolumab currently approved in the European Union requires testing of PD-L1 (programmed cell death ligand 1) protein expression by immunochemistry in tumor tissue. Focusing on MIBC patients at high risk of recurrence, new questions arise regarding the implementation and interpretation of PD-L1 testing. An interdisciplinary group of experts from Germany has discussed relevant issues from a clinicopathological point of view and developed practical recommendations to facilitate the implementation of validated and quality-assured PD-L1 testing for the approved indications in daily clinical practice.	bladder
Observational study of in-hospital mortality risk from bladder cancer: Five years of experience at a tertiary referral hospital in Indonesia.	Bladder cancer (BC) is a neoplasm arising from the bladder. It requires appropriate management and its prognosis depends on many factors. This study aimed to analyze the factors that influence outcomes in BC management. This was a retrospective study. Data were collected at one of Indonesia's largest tertiary referral hospitals. All patients diagnosed with BC from January 2019 to December 2023 were included. The outcome measured was survival or death. Statistical analysis was conducted using SPSS version 26.0 software. The study included 219 patients with a median age of 57.97 years, of which 99 (45.2 %) patients died. In a bivariate analysis, sex, active smoking status, Karnofsky score, metastasis status, chronic kidney disease, type 2 diabetes mellitus, chemotherapy, radiotherapy, and alternative medicine were found to affect mortality status. Based on multivariate analysis, the route of admission (odds ratio [OR] 0.19), irregular visit (OR 6.21), metastasis (OR 3.58), radiotherapy (OR 21.12), and traditional medicine (OR 0.21) were independent factors of in-hospital mortality. The mortality rate for BC was considerably high. Irregular visits, metastasis, type 2 diabetes, and radiotherapy were independent risk factors for mortality.	bladder
The association between variant histology and prognostic, histomorphological and clinical aspects of bladder urothelial carcinoma.	"This study underscores the imperative consideration of histological subtypes and divergent differentiation in accurately estimating bladder urothelial carcinoma prognosis and guiding treatment decisions. A comparative analysis was conducted, examining clinical, histological, and prognostic factors between conventional urothelial carcinoma and urothelial carcinoma with variant histology in a clinical sample. A retrospective analysis of slides and other clinicopathologic data was conducted these cases, with an emphasis on key diagnostic elements. We examined 829 cases of urothelial carcinoma of the bladder, comprising of 744 transurethral resection (TUR) and 85 radical cystectomy (RS) specimens, an analysis that showed that 80.5 % (667 cases) were conventional urothelial carcinoma (CUC) and that 19.5 % (162 cases) exhibited variant histology (hereafter ""urothelial carcinoma with subtype histology"" [UCSH]). TNM classifications for the RS cases were as follows: 2 cases were stage group 0a, 11 stage group 1, 16 stage group 2, 45 stage group 3a, 2 stage group 3b, 1 stage group 4a, and 8 stage group 4b. Only 2 of the RS cases were found to be non-invasive. Among 744 TUR specimens, 387 were found to have a non-invasive tumor whereas 357 had invasive tumors. The most prevalent subtype in the UCSH group was urothelial carcinoma with squamous differentiation, accounting for 54.3 % (88 cases). Notably, 8.02 % (13 cases) exhibited more than one histological subtype. Papillary configuration, histological grade, lamina propria, muscularis mucosa and serosa invasion, lymphovascular invasion, presence of urothelial carcinoma in situ, and overall survival significantly differed between the UCSH and CUC groups (p < 0.05). However, mean age, gender, tumor size, lymphocytic response, disease-free survival, and survival status did not differ significantly (p > 0.05). Among the UCSH group, lower levels of papillary configuration, higher histological grade, higher degree of lamina propria, muscularis mucosa and serosa invasion, and the presence of carcinoma in situ corresponded to higher percentage of histological subtype morphology (p < 0.05). No significant difference in survival status was observed between the groups with and without subtype histology (p = 0.083). This study found that clinical and histopathological prognostic factors associated with a more aggressive disease were linked to the presence and percentage of histological subtypes. Recognizing histological subtype is crucial for treatment decisions and prognosis prediction in urothelial carcinoma cases with these subtypes."	bladder
The Impact of Fibroblast Growth Factor Receptor Alterations in Clinical Outcomes of Patients With Advanced Urothelial Carcinoma: Real-World Data From a Latin American Population.	INTRODUCTION: Fibroblast growth factor receptor (FGFR) mutations and fusions are relevant biomarkers in metastatic urothelial carcinoma (mUC). However, the prevalence of genomic alterations and their impact on clinical outcomes in a Latin American population remains unknown. This study aimed to explore the prevalence of FGFR mutations and/or fusions in patients with mUC in Latin America (LATAM) and its association with clinicopathological characteristics, Bellmunt's prognostic model, and survival outcomes. PATIENTS AND METHODS: A multicenter retrospective cohort study from 2016 to 2019 of patients with mUC from several LACOG LATAM institutions. FGFR alterations were analyzed by real-time PCR and/or next-generation sequencing in tumor samples and clinicopathologic characteristics and survival outcomes data were collected. The prevalence of FGFR, patient characteristics, and treatment in real-world settings were summarized. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate the associations of FGFR mutation and/or fusion status with median overall survival (mOS), median time to treatment failure (mTTF), and clinicopathological characteristics. RESULTS: In total, 222 patients were screened. Of these, 196 patients were considered eligible and were included in the analysis. FGFR mutations and/or fusions were found in 35 (17.9%) patients. There was no statistical difference in mOS and mTTF in FGFR-altered and non-altered patients (13.1 vs. 16.8 months, P = .20 and 3.9 vs. 4.1 months, P = .96, respectively). Bellmunt's prognostic model correctly predicted overall survival (P = .049). CONCLUSIONS: This is the largest study evaluating the prevalence of FGFR alterations in patients with mUC in the LATAM population. FGFR alterations in mUC were found in 17.9% of the patients, and the presence of this biomarker was not associated with OS. We validated Bellmunt's prognostic model in this cohort.	bladder
Next-generation sequencing has diagnostic utility in challenging small/flat urothelial lesions.	Small/flat urothelial lesions are challenging and currently available ancillary immunohistochemistry testing often cannot reliably distinguish between reactive lesions and urothelial carcinoma (UCa). UCa has a characteristic molecular profile, but small/flat urothelial lesions are typically considered too small to perform next generation sequencing (NGS). Herein, we present our institution's experience with utilizing comprehensive DNA-based NGS to evaluate small/flat urothelial lesions (n = 13 cases). NGS was ordered on 7/13 small/flat urothelial lesions initially diagnosed as urothelial atypia, ordered by the pathologist to aid in further diagnosis; the remaining 6/13 cases were diagnosed as urothelial carcinoma in situ (uCIS), ordered by a treating oncologist. The test was considered as adding value if it yielded pathogenic or likely pathogenic alterations previously associated with urothelial carcinoma in the literature. Macroscopic dissection was determined necessary in all cases and obtained either by scraping (7), punch biopsy (5) or scooping (1) of paraffin tissue blocks. In 4/13 cases, tumor content was considered low (<25%); in 2/13 cases, DNA quantity yield was considered below optimal (<250 ng); all cases met required DNA quantity for testing (>50 ng). Mean target coverage ranged: 498 to 985 (optimal >500 reads). NGS testing identified mutations compatible with urothelial carcinoma in all 7 cases initially diagnosed as atypical; and in one case, the tumor recurred as a lung metastasis. All 6 uCIS had NGS testing results concordant with UCa. In conclusion, despite small sample quantity with low tumor content and DNA concentration yield, NGS testing with appropriate methodology can be considered in the setting of small/flat urothelial lesions to aid in diagnosis or per oncologist request and yield interpretable results.	bladder
Urachal Carcinoma: Insights From a National Database.	INTRODUCTION: Urachal carcinoma (UrC) is a rare, nonurothelial malignancy, comprising less than 1% of all bladder cancers. It usually affects males in their fifth to sixth decade and is often diagnosed at an advanced stage with metastasis. This study examines UrC population characteristics and management. METHODS: We identified UrC patients from bladder biopsies or TURB in the PearlDiver Mariner database (2010-2022). Descriptive statistics detailed patient characteristics. Student's T-Tests compared ages for partial vs. radical cystectomy, and Fisher's exact test compared SDOH presence. Significance was set at P < .05. Analyses used R version 3.6.0 within PearlDiver's software. RESULTS: Among 2475 UrC patients (mean age 69.2 ± 9.2 years, 73.1% men), most were in the south (36.5%), outpatient settings (84.5%), and privately insured (65.3%). A total of 418 (16.2%) had at least 1 SDOH. Imaging before diagnosis was used in 65.74% of patients, primarily ultrasound. Smoking was present in 54.5%, diabetes in 42.9%, and obesity in 25.2%. After diagnosis, 1246 (50.34%) had localized disease; 407 underwent radical cystectomy and 330 partial cystectomy. Patients undergoing radical cystectomy were older (66.74 ± 8.13 years) compared to those undergoing partial cystectomy (60.55 ± 12.92 years) (P < .001), with SDOH factors more prevalent in the partial cystectomy group (P = .03). CONCLUSION: UrC is a rare, often advanced-stage cancer predominantly affecting older men. Our study shows a trend towards partial cystectomy for localized UrC. Further research is needed to personalize surgery and integrate multidisciplinary approaches for better outcomes.	bladder
[New therapeutic approaches for non-muscle invasive bladder cancer-is organ preservation also possible after BCG (Bacillus Calmette Guérin)?].	Bacillus Calmette-Guérin (BCG) therapy is the standard of care in the treatment of high-risk non-muscle invasive bladder cancer (NMIBC). In the absence of a response to BCG and persistent high-grade disease, cystectomy is recommended depending on the clinical risk. A variety of targeted therapy approaches, which aim at immune- and gene-based molecular targets, such as PD-(L)1 and FGFR, are currently being investigated in randomized studies for BCG-unresponsive NMIBC. Furthermore, novel forms of application for instillation therapy, such as the TAR device, in combination with gemcitabine or erdafitinib are being investigated in clinical trials in order to extend the duration of action of the active substance on the urothelium. Thus, there are now many developments that could make bladder-preserving therapy with comparable survival data possible as an alternative to BCG or in the event of BCG failure. In the future, it will be necessary to clarify how BCG response can be predicted by using molecular markers and how to define risk groups that should primarily be given an alternative therapy to BCG.	bladder
Asiaticoside enhances the effect of propofol on the invasion, ferroptosis and immune escape of bladder cancer.	Bladder cancer is a highly prevalent malignancy. Asiaticoside (AC), a triterpenoid derivative, exhibits antitumor effect on different tumors. This study aimed to explore the role and mechanism of AC on bladder cancer. J82 and T24 cells were treated with AC and/or propofol, and nude mice were subcutaneously administrated with T24 cells. The effect and mechanism of AC and/or propofol were explored by cell counting kit-8, transwell, flow cytometry, enzyme-linked immunosorbent assay, immunohistochemistry and western blot assays both in vitro and in vivo. Cell viability of J82 and T24 cells was inhibited by AC with a IC50 value of 2.43 μM and 2.16 μM, and by propofol with a IC50 value of 42.51 μM and 48.37 μM, respectively. AC or propofol alone decreased cell proliferation, invasion, and immune escape with the increased ferroptosis, as well as downregulating the level of the PI3K/AKT pathway in both animal and cell experiments. The effect of propofol on the above-mentioned indicators was further enhanced with the co-treatment of AC in vitro and in vivo. Taken together, AC promoted the ameliorative effect of propofol on bladder cancer involved in PI3K/AKT pathway.	bladder
Adverse drug reactions of intravesical instillation therapy for bladder cancer: based on FDA adverse event reporting system.	BACKGROUND: Intravesical chemotherapy and immunotherapy are common adjuvant treatments for non-muscle invasive bladder cancer post-surgery. Analyzing adverse events linked to these therapies, can assist in clinical decision-making and risk assessment. STUDY DESIGN AND METHODS: Disproportionality analysis was conducted to analyze data from the Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the first quarter of 2024, exploring potential positive signals between Bacillus Calmette-Guérin, mitomycin-C, epirubicin, gemcitabine, and adverse events. RESULTS: The database retrieved 2018, 140, 31, and 85 adverse event reports associated with Bacillus Calmette-Guérin, mitomycin-C, epirubicin, and gemcitabine, respectively. Adverse reactions not mentioned in the label, such as aortic aneurysm and ocular congestion, were observed in preferred term level related to Bacillus Calmette-Guérin. Mitomycin-C exhibited specificity in skin and subcutaneous tissue diseases not reflected in the package insert. Gemcitabine-induced adverse drug reactions showed signals in vascular and lymphatic diseases meeting the screening criteria of all 4 indicators, with capillary leakage syndrome being the preferred term with the highest signal intensity. CONCLUSION: This study observed new adverse event signals, providing important assistance for drug selection in adjuvant therapy for non-muscle invasive bladder cancer postoperatively.	bladder
Integrative Drug Screening and Multiomic Characterization of Patient-derived Bladder Cancer Organoids Reveal Novel Molecular Correlates of Gemcitabine Response.	BACKGROUND AND OBJECTIVE: Predicting response to therapy for each patient's tumor is critical to improving long-term outcomes for muscle-invasive bladder cancer. This study aims to establish ex vivo bladder cancer patient-derived organoid (PDO) models that are representative of patients' tumors and determine the potential efficacy of standard of care and curated experimental therapies. METHODS: Tumor material was collected prospectively from consented bladder cancer patients to generate short-term PDO models, which were screened against a panel of clinically relevant drugs in ex vivo three-dimensional culture. Multiomic profiling was utilized to validate the PDO models, establish the molecular characteristics of each tumor, and identify potential biomarkers of drug response. Gene expression (GEX) patterns between paired primary tissue and PDO samples were assessed using Spearman's rank correlation coefficients. Molecular correlates of therapy response were identified using Pearson correlation coefficients and Kruskal-Wallis tests with Dunn's post hoc pairwise comparison testing. KEY FINDINGS AND LIMITATIONS: A total of 106 tumors were collected from 97 patients, with 65 samples yielding sufficient material for complete multiomic molecular characterization and PDO screening with six to 32 drugs/combinations. Short-term PDOs faithfully represent the tumor molecular characteristics, maintain diverse cell types, and avoid shifts in GEX-based subtyping that accompany long-term PDO cultures. Utilizing an integrative approach, novel correlations between ex vivo drug responses and genomic alterations, GEX, and protein expression were identified, including a multiomic signature of gemcitabine response. The positive predictive value of ex vivo drug responses and the novel multiomic gemcitabine response signature need to be validated in future studies. CONCLUSIONS AND CLINICAL IMPLICATIONS: Short-term PDO cultures retain the molecular characteristics of tumor tissue and avoid shifts in expression-based subtyping that have plagued long-term cultures. Integration of multiomic profiling and ex vivo drug screening data identifies potential predictive biomarkers, including a novel signature of gemcitabine response. PATIENT SUMMARY: Better models are needed to predict patient response to therapy in bladder cancer. We developed a platform that uses short-term culture to best mimic each patient's tumor and assess potential sensitivity to therapeutics.	bladder
Exposures and Bladder Cancer Risk Among Military Veterans: A Systematic Review and Meta-analysis.	OBJECTIVE: To investigate potential carcinogenic exposures in military personnel that are implicated in the development of bladder cancer. METHODS: This systematic review aimed to evaluate the association between specific military exposures and bladder cancer risk among veterans. PubMed, Scopus, and Ovid MEDLINE databases were searched in December 2023 for relevant articles. Inclusion criteria comprised retrospective cohort studies, reviews, and observational studies documenting bladder cancer incidence among military populations exposed to specific agents. A total of 25 studies, involving 4,320,262 patients, met the inclusion criteria. Data extraction followed PRISMA guidelines, and a random-effects model was used for data synthesis. RESULTS: The meta-analysis revealed significant associations between exposure to Agent Orange (HR 1.17 [95% CI: 1.01-1.36], P < .00001) and depleted uranium (HR 2.13 [95% CI: 1.31-3.48], P = .002) with increased bladder cancer risk among veterans. Contaminated drinking water showed a trend towards increased risk (HR 1.25 [95% CI: 0.97-1.61], P = .08). CONCLUSION: The findings suggest a possible association between specific military exposures and heightened bladder cancer risk among veterans, emphasizing the necessity for targeted screening protocols and preventive measures. Further research is essential to identify specific carcinogenic agents and prevalence of exposures among veterans, enabling more effective prevention and management strategies.	bladder
Exploration of biomarkers for nursing physical examination early screening of multiple tumors.	Nursing and physical examination early screening of multiple tumors is helpful to find tumors early, so as to improve the cure rate. Studying its molecular mechanisms is urgent. By logging into gene expression omnibus database, we found laryngeal cancer dataset GSE127165, bladder cancer dataset GSE65635, oral cancer dataset GSE146483, obtain differentially expressed genes, subsequently, weighted gene co-expression network analysis, protein-protein interaction networks, functional enrichment analysis, immune infiltration analysis, survival analysis, comparative toxicogenomics database analysis were conducted. Draw a heatmap of gene expression. Use targetScan to search for miRNA information about core DEG. Got 53 differentially expressed genes. In GOKEGG analysis, they were clustered in cell cycle processes, spindle poles, and protein serine/threonine/tyrosine kinase activity cell cycle, transcriptional dysregulation in cancer, RIG-I-like receptor signaling pathway, P53 signaling pathway. Protein-protein interaction analysis screened out 5 genes (NEK2, BUB1, HMMR, TTK, CCNB2). Cyclin B2 (CCNB2) and budding uninhibited by benzimidazole 1 (BUB1) were highly expressed in laryngeal cancer, bladder cancer, oral cancer. Comparative toxicogenomics database analysis found that core genes (CCNB2, BUB1) are associated with tumors, necrosis, and inflammation. Related miRNA of CCNB2 gene is hsa-miR-670-3p; related miRNAs of BUB1 gene are hsa-miR-5688, hsa-miR-495-3p. CCNB2 and BUB1 exhibit high expression in laryngeal cancer, bladder cancer, and oral cancer, suggesting their potential as molecular targets for precision therapy in these cancers.	bladder